1.Dipsacus asper Treats Alzheimer's Disease in Caenorhabditis elegans by Regulating PPARα/TFEB Pathway
Mengmeng WANG ; Jianping ZHAO ; Limin WU ; Shuang CHU ; Yanli HUANG ; Zhenghao CUI ; Yiran SUN ; Pan WANG ; Hui WANG ; Zhenqiang ZHANG ; Zhishen XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):104-114
ObjectiveTo investigate the anti-Alzheimer's disease (AD) effect of Dipsacus asper(DA) in the Caenorhabditis elegans model, and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α (PPARα)/transcription factor EB (TFEB) pathway. MethodsFirst, transgenic AD C. elegans individuals were assigned into the blank control, model, positive control (WY14643, 20 µmol·L-1), and low-, medium-, and high-dose (100, 200, and 400 mg·L-1, respectively) DA groups. The amyloid β-42 (Aβ42) formation in the muscle cells, the paralysis time, and the deposition of amyloid β-protein (Aβ) in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ, LC3I, LAMP2, and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα, and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain (LBD). ResultsCompared with the model group, the positive control group and 200 and 400 mg·L-1 DA groups showed prolonged paralysis time (P<0.05), and all the treatment groups showed decreased Aβ deposition in the head (P<0.01). DA within the concentration range of 50-500 mg·L-1 did not affect the viability of BV2 cells. In addition, DA enhanced the autophagy flux (P<0.05), up-regulated the mRNA levels of beclin1, Atg5, LAMP2, and CLN2 (P<0.05, P<0.01), promoted the nuclear translocation of TFEB (P<0.05), increased LAMP2 expression and autophagy flux (P<0.05, P<0.01), and enhanced the transcriptional activities of PPARα and TFEB (P<0.01). The positive control group and 200 and 400 mg·L-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus (P<0.01). UPLC-MS detected nine known compounds of DA, from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.
2.Pharmacokinetic Analysis of Ziyuglycoside Ⅰ in Normal and Acute Kidney Injury Rats
Yunhui ZHANG ; Yanli LIU ; Qiongming XU ; Shuding SUN ; Hongjin ZHU ; Di ZHAO ; Suxiang FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):203-210
ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry(UPLC-Orbitrap Fusion Lumos Tribrid-MS), the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration, and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group, the model group received intraperitoneal cisplatin(10 mg·kg-1) to establish the acute kidney injury model, the normal group was given the same volume of saline. After successful modeling, rats in the normal and model groups were randomly divided into the normal low, medium and high dose groups(2.5, 5, 7.5 mg·kg-1) and the model low, medium and high dose groups(2.5, 5, 7.5 mg·kg-1), 6 rats in each group, and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then, the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS, and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software, and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ, its concentration increased first and then decreased, and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve(AUC0-t) and mean retention time(MRT0-t) of normal and model rats increased with the increased dose, and the clearance(CL) decreased with the increasing dose. Compared with the normal group, the AUC0-t was significantly increased(P<0.01), peak concentration(Cmax) and CL decreased in model rats at different doses, indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats, which may be due to the change of the body environment in the pathological state, then lead to changes in absorption and metabolic processes.
3.Palpitations, Shortness of Breath, Weakness in Limbs, Edema, and Dyspnea: A Rare Inflammatory Myopathy with Positive Aniti-mitochondrial Antibodies and Cardiac Involvement
Chunsu LIANG ; Xuchang ZHANG ; Ning ZHANG ; Lin KANG ; Xiaohong LIU ; Jiaqi YU ; Yingxian LIU ; Lin QIAO ; Yanli YANG ; Xiaoyi ZHAO ; Ruijie ZHAO ; Na NIU ; Xuelian YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):248-255
This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.
4.Analysis of the current status and influencing factors of cognitive function and sleep quality of elderly people in Shanghai community
Yanli ZHANG ; Meng WANG ; Xuechun WANG ; Shanshan HUANG ; Jiaoqi REN ; Houguang ZHOU
Chinese Journal of Clinical Medicine 2025;32(1):58-64
Objective To analyze the cognitive function and sleep quality of the elderly in Shanghai community, and explore the related influencing factors. Methods A stratified cluster random sampling method was used to select 8 community health centers in Shanghai for a questionnaire survey, including 3 677 elderly individuals who completed the “Comprehensive Health Status Survey of Elderly Residents in Shanghai” from September 2023 to November 2023. Basic information of the elderly was collected, including age, gender, education level, smoking, drinking, mahjong playing behavior, and exercise habits. The Pittsburgh sleep quality index (PSQI) was used to assess the sleep quality of the elderly, subjective cognitive decline (SCD) self-assessment questionnaire and Mini-Mental State Examination (MMSE) were used to evaluate cognitive function, while the Hamilton Anxiety Scale (HAMA) and patient health questionnaire-9 (PHQ-9) were used to assess anxiety and depression levels, and the mini nutritional assessment (MNA) was used to evaluate nutritional status. According to the MMSE scores, the elderly were divided into three groups: no cognitive impairment (MMSE ≥ 27), mild cognitive impairment (MMSE 21-26), and moderate to severe cognitive impairment (MMSE ≤ 20). The general data, lifestyle habits, and scale scores of the three groups were compared. Ordered logistic regression was used to analyze the influencing factors of sleep quality. Results There were statistically significant differences in age, gender, waist circumference, body mass index (BMI), education level, pet ownership, smoking, drinking, mahjong playing behavior, exercise habits, and scale scores among the three groups (P<0.05). Logistic regression analysis showed that age, waist circumference, gender, drinking habits, mahjong playing behavior, and chronic comorbidities are influencing factors for the PSQI grading in the elderly (P<0.05). The MMSE score (OR=1.037, P=0.001), SCD score (OR=1.123, P<0.001), HAMA score (OR=1.183, P<0.001), PHQ-9 score (OR=1.249, P<0.001) are positive influencing factors for PSQI grading, while the MNA score is a negative influencing factor (OR=0.960, P=0.037). Conclusions Advanced age, female gender, low education level, no pet ownership, no mahjong playing behavior, no exercise habits, and poor sleep quality are risk factors for cognitive impairment in the elderly. Advanced age, female gender, no mahjong playing behavior and poor nutritional status are influencing factors for poor sleep quality in the elderly, and severe comorbidities, anxiety, depression, and subjective decline in cognitive function all affect sleep quality.
5.Impact of vestibular dysfunction on cognitive function
Ruiqi ZHANG ; Yanli ZHAO ; Dongmei ZHANG ; Wenyan LI ; Peixia WU
Chinese Journal of Clinical Medicine 2025;32(2):218-224
Objective To investigate the impact of vestibular dysfunction on various domains of cognitive function, providing a basis for developing comprehensive vestibular-cognitive intervention strategies. Methods A total of 33 patients with confirmed unilateral vestibular dysfunction treated at Eye & ENT Hospital, Fudan University between June 2024 and December 2024. Vestibular function was assessed using vestibular evoked myogenic potential (VEMP), caloric testing, video head impulse test (vHIT), and sensory organization test (SOT). Cognitive function was evaluated using mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Stroop color-word test, trail making test (TMT), and auditory verbal learning test (AVLT). Subjective symptoms were assessed using dizziness handicap inventory (DHI). Results In the vestibular function assessment of patients, abnormalities in caloric testing, utricle VEMP and saccule VEMP results were most common, with rates of 87.9%, 57.6%, and 66.7%, respectively; SOT abnormality primarily characterized by impaired vestibular function (21.2%). Spearman correlation analysis showed age, years of education, hearing ability, and emotional state were associated with overall or specific domains of cognitive function in patients. Greater vestibular dysfunction severity was associated with longer TMT-A time (r=0.443,P=0.010), most severe damage of short-term (r=-0.405,P=0.019) and long-term delayed recalls (r=-0.537,P=0.001). Patients with 31-60 of DHI scores showed longer TMT-A time than patients with 0-30 of DHI scores (P=0.033). Conclusions Patients with vestibular dysfunction exhibit significant impairment in low-frequency semicircular canal and utricle function, which affects attention allocation, information processing speed, and memory performance in cognitive tasks.
6.Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive
Haolong LI ; Song LIU ; Xu WANG ; Xinxin FENG ; Siyu WANG ; Yanli ZHANG ; Fengchun ZHANG ; Li WANG ; Tengda XU ; Yongzhe LI
Clinical and Molecular Hepatology 2025;31(2):474-488
Background:
s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals.
Methods:
A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC.
Results:
A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917.
Conclusions
This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.
7.Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive
Haolong LI ; Song LIU ; Xu WANG ; Xinxin FENG ; Siyu WANG ; Yanli ZHANG ; Fengchun ZHANG ; Li WANG ; Tengda XU ; Yongzhe LI
Clinical and Molecular Hepatology 2025;31(2):474-488
Background:
s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals.
Methods:
A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC.
Results:
A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917.
Conclusions
This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.
8.Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive
Haolong LI ; Song LIU ; Xu WANG ; Xinxin FENG ; Siyu WANG ; Yanli ZHANG ; Fengchun ZHANG ; Li WANG ; Tengda XU ; Yongzhe LI
Clinical and Molecular Hepatology 2025;31(2):474-488
Background:
s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals.
Methods:
A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC.
Results:
A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917.
Conclusions
This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.
9.Investigation of parasitic infection in food on market in Qingpu District of Shanghai during 2015‒2023
Chengcheng WANG ; Changpo LIN ; Yanli DAI ; Zhicheng ZHANG ; Qunqun LIU ; Yadong MA ; Xueqin YU
Shanghai Journal of Preventive Medicine 2025;37(3):260-264
ObjectiveTo understand the status of parasitic infection in the food sold on market in Qingpu District of Shanghai, and to provide an evidence for the development of prevention and control strategies for parasitic infection applicable to Qingpu District. MethodsAquatic products, meat products and other foodstuffs sold on online shops, at farm product markets, supermarkets/foodstores and restaurants were sampled in Qingpu District, Shanghai, during 2015‒2023, based on the administrative division of Qingpu District. The parasitic infection in the food samples were examined using pressing method and digestion for detecting metacercariae in freshwater products and pickled products, using dissection microscopy for Anisakis larvae in seawater products, Taenia cysticercus and Trichinella encysted larvae in meat products. ResultsA total of 1 079 samples of food products were examined during 2015‒2023, with a total parasite infection rate of 13.44%. The total parasite infection rate of freshwater fish products was 3.40% (16/471), and the difference of parasite infection rates between different freshwater fish species was statistically significant (χ2=229.609, P=0.001). The total infection rate of Clonorchis sinensis was 3.18% (15/471), which had been detected in Pseudorasbora parva, Cyprinidae rhodeus, and Carassius auratus, with a positive rate of 77.78% (7/9), 50.00% (5/10) and 3.90% (3/77), respectively. Metorchis orientalis was detected in in Pseudorasbora parva, with a positive rate of 33.33% (3/9). The positive rate of Gnathostoma spinigerum (third-stage larvae) was 0.81%. Paragonimus metacercariae were not detected in the freshwater shrimps and crabs. The infection rate of seawater fish products was 26.46%. The difference of parasite infection rate in seawater fishes was statistically significant (χ2=109.181, P=0.001). A total of 53 pork and beef samples were tested, none was detected with Trichinella larva cysts, Taenia solium metacercariae, and Taenia saginata metacercariae. The total infection rate of pickled yellow mud snail products was 58.11% (43/74). Paragonimus metacercariae was not detected in any of the pickled aquatic product samples. ConclusionThere are different degrees of parasitic infection in freshwater products, seawater products and pickled aquatic products in Qingpu District of Shanghai. The risk of parasite infection from raw or undercooked foods is high. Health education on healthy dietary practices such as throughly cooked food should be strengthened for local residents.
10.Study on the current status of emergency management for severe mental disorders in Shanghai
Xiaolei GE ; Yi ZHU ; Chunmei CHEN ; Youwei ZHU ; Yanli LIU ; Jun CAI ; Weibo ZHANG ; Fei XIE
Shanghai Journal of Preventive Medicine 2025;37(3):276-281
ObjectiveTo investigate the current status of emergency management for severe mental disorders in Shanghai, and to provide countermeasures and suggestions for the establishment of a sound emergency management system for severe mental disorders and the enhancement of emergency management capability. MethodsA questionnaire survey and qualitative interviews were used to conduct an investigation into the emergency management in 17 district-level mental illness prevention and control institutions in Shanghai, which includes the basic situation of emergency management for severe mental disorders, the construction of emergency response teams and personnel, emergency preparedness drills and training, emergency management plans and rules and regulations, and problems encountered in emergency management. ResultsIn terms of emergency management mechanism and basic situation, resources such as personnel allocation, security funds and green channel were well equipped in each district-level mental illness prevention and control institution in Shanghai. However, the equipment of some hardware facilities was still insufficient to some extent. Therefore, further improvement on the emergency management mechanism for severe mental disorders was needed. With regard to the construction of emergency team and personnel allocation, the majority were those aged between 35‒<45 years old, with a bachelor’s degree, and more than 10 years of working experience. For example, 90.27% staff in district-level mental illness prevention and control institution had a bachelor’s degree or above, which was higher than that among the staff in community-level (73.60%); staff majored in clinical medicine in district-level institution accounted for the proportion at 52.71%, higher than that among the staff in community-level (28.86%); 57.24% staff in district-level institution had an intermediate professional title, higher than that among the staff in community-level (42.28%); and 69.90% staff in district-level institution had more than 10 years of working experience, higher than that among the staff in community-level (43.62%). In the aspect of emergency drills and training, all district-level mental illness prevention and control institutions in Shanghai had a high demand for emergency training, and the weak aspects mainly focused on lack of emergency service protocols, skills of addressing technical challenges, and construction of effectiveness evaluation system. Moreover, the teaching methods were primarily centered on case analysis, simulation drills, interactive discussions, and so forth. Concerning emergency management plans and rules and regulations, all districts in Shanghai had relatively established well-developed systems for emergency response plans, emergency response leadership groups, and emergency response operational task forces for severe mental disorders. About half of the institutions had established other rules and regulations related to emergency management of severe mental disorders in addition to emergency plans. ConclusionShanghai has initially established an emergency management system for severe mental disorders, but it is still fragile in specialized training for emergency management of severe mental disorders, construction of emergency management mechanisms, and the building-up of grassroots emergency teams. Further priorities should include strengthening emergency management training, enhancing the construction of emergency management personnel teams, and gradually establishing a more comprehensive and integrated emergency management mechanism for severe mental disorders.

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